Immunological Basis of Egg Allergy

鸡蛋过敏的免疫学基础

• 批准号: 6922221
• 负责人: Anna Halina Nowak-Wegrzyn
• 金额: $ 12.87万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6922221
• 关键词: adolescence (12-20); antibody specificity; atopic dermatitis; child (0-11); clinical research; dietary constituent; egg proteins; epitope mapping; feces analysis; food hypersensitivity; gastrointestinal absorption /transport; heat; human subject; immune response; immunogenetics; immunoglobulin E; nutrition related tag; patient oriented research

DESCRIPTION (provided by applicant): My immediate goal is to acquire skills necessary for an independent career in patient-oriented research. I need training in design and conduct of patient-oriented research as well in immunology laboratory techniques. My long-term objectives are to stablish myself as an investigator in the field of novel therapies for food allergy. I am confident that at Mount Sinai I am in the nurturing environment committed to my success. I will receive highest-quality mentoring from Dr. Hugh A. Sampson and will have strong support from the Food Allergy Laboratory with access to the state-of-the-art equipment. Clinical Research Training Program to develop solid skills in responsible conduct, design, and analysis of clinical research. Egg allergy is one of the most common food allergies in children. Allergic reactions are more frequently caused by egg white than by egg yolk proteins and ovomucoid is the dominant allergen. Previous studies have demonstrated that children with persistent egg allergy have significantly higher concentrations of IgE-anti-ovomucoid antibodies than those who develop tolerance to egg and those with high IgE-binding activity to pepsin-treated ovomucoid are unlikely to outgrow egg white allergy. We propose to test the following hypotheses: 1. Specific Aim # 1: Test the hypothesis that egg-allergic children who can ingest extensively heated (baked) egg proteins without experiencing allergic symptoms lack IgE antibodies to sequential egg epitopes compared with children that react to extensively heated egg and possess IgE antibodies to sequential egg epitopes. Children with egg allergy will be challenged to baked products containing cooked egg proteins. Challenge outcome will be compared to epitope recognition. Children tolerating egg in baked goods will be randomized to receive egg-free or egg containing diet, and monitored for 48 months. Egg protein- and epitope- specific IgE and IgG antibodies, intestinal permeability, and growth will be monitored. 2. Specific Aim # 2: Test the hypothesis that children with more diverse egg IgE epitope recognition patterns have functional consequences on effector cells resulting in more severe reactions and more persistent egg allergy. IgE and IgG antibody avidity and epitope specificity to the two major egg white allergens (ovomucoid and ovalbumin) will be monitored on a yearly basis by peptide array in 90 patients with IgE-mediated egg allergy over 48 months and will be correlated with clinical reactivity to egg determined by double-blinded placebo controlled egg challenges. Antibody avidity will be assessed with thiocyanate disruption. The effector function of IgE antibodies will be assessed by basophil release test with the use of passively sensitized FceRI-transfected rat basophil leukemia cell line stimulated with native and heat-inactivated egg proteins. 3. Specific Aim# 3: Test the hypothesis that egg-specific IgE antibodies facilitate uptake of egg allergen in the gastrointestinal tract and that the concentration of fecal egg-lgE antibody correlates with intestinal permeability and clinical reactivity to egg in children with egg allergy. We postulate that egg-allergic children have anti-egg IgE antibodies detectable in stool, and that luminal anti-egg IgE antibodies facilitate the uptake of egg allergen, resulting in clinical symptoms and increased intestinal permeability. Stool samples will be obtained prior to and following each oral egg challenge (at multiple time points over 48 months) in children participating in a clinical trial described in Aim # 1. Total and egg-specific IgE, egg-lgE and egg-specific IgG will be determined in each stool sample and correlated with clinical outcome of the oral egg challenge. Intestinal permeability will be tested prior to baseline egg challenges in all children participating in Aim # 1 and following oral egg challenges in a smaller subset of patients. Intestinal permeability will also be measured at 3 and 12 months, and correlated with oral egg challenge outcome, fecal and serum anti-egg IgE and anti-egg IgG antibody levels.

描述（由申请人提供）：我的近期目标是获得以患者为导向的研究中独立职业所需的技能。我需要设计和进行以患者为导向的研究以及免疫学实验室技术方面的培训。我的长期目标是使自己成为食物过敏新疗法领域的研究者。我相信，在西奈山，我的培养环境致力于我的成功。我将获得 Hugh A. Sampson 博士的最高质量指导，并将获得食物过敏实验室的大力支持，并使用最先进的设备。临床研究培训计划，旨在培养负责任地进行、设计和分析临床研究的扎实技能。鸡蛋过敏是儿童最常见的食物过敏之一。过敏反应更常见的是由蛋清引起的，而不是由蛋黄蛋白引起的，卵类粘蛋白是主要的过敏原。先前的研究表明，患有持续性鸡蛋过敏的儿童的 IgE 抗卵类粘蛋白抗体浓度明显高于那些对鸡蛋产生耐受性的儿童，而那些对胃蛋白酶处理的卵类粘蛋白具有高 IgE 结合活性的儿童不太可能摆脱蛋清过敏。 我们建议检验以下假设： 1. 具体目标#1：测试以下假设：与对高度加热的鸡蛋有反应并拥有 IgE 抗体的儿童相比，可以摄入高度加热（烘烤）的鸡蛋蛋白而不会出现过敏症状的鸡蛋过敏儿童缺乏针对连续鸡蛋表位的 IgE 抗体。连续的卵表位。对鸡蛋过敏的儿童将面临含有熟鸡蛋蛋白的烘焙产品的挑战。挑战结果将与表位识别进行比较。能够耐受烘焙食品中鸡蛋的儿童将被随机分配接受无鸡蛋或含鸡蛋饮食，并进行为期 48 个月的监测。将监测卵蛋白和表位特异性 IgE 和 IgG 抗体、肠道通透性和生长。 2. 具体目标#2：检验以下假设：鸡蛋 IgE 表位识别模式更加多样化的儿童会对效应细胞产生功能性影响，从而导致更严重的反应和更持久的鸡蛋过敏。将每年通过肽芯片对 90 名 IgE 介导的鸡蛋过敏患者进行超过 48 个月的监测，对两种主要蛋清过敏原（卵类粘蛋白和卵清蛋白）的 IgE 和 IgG 抗体亲合力和表位特异性进行监测，并将与临床反应性相关联。通过双盲安慰剂对照鸡蛋挑战确定鸡蛋。将通过硫氰酸盐破坏来评估抗体亲合力。 IgE 抗体的效应功能将通过嗜碱性粒细胞释放测试进行评估，使用被动致敏的 FceRI 转染的大鼠嗜碱性粒细胞白血病细胞系，并用天然和热灭活的卵蛋白刺激。 3. 具体目标#3：检验以下假设：鸡蛋特异性 IgE 抗体促进胃肠道摄取鸡蛋过敏原，并且粪便鸡蛋 IgE 抗体的浓度与鸡蛋过敏儿童的肠道通透性和对鸡蛋的临床反应性相关。 我们假设鸡蛋过敏儿童在粪便中可检测到抗鸡蛋 IgE 抗体，并且腔内抗鸡蛋 IgE 抗体促进鸡蛋过敏原的摄取，导致临床症状和肠道通透性增加。将在参与目标 # 1 中描述的临床试验的儿童的每次口服鸡蛋挑战之前和之后（在 48 个月内的多个时间点）获取粪便样本。总和鸡蛋特异性 IgE、鸡蛋-IgE 和鸡蛋特异性 IgG将在每个粪便样本中进行测定，并与口服鸡蛋挑战的临床结果相关。将在参与目标＃1的所有儿童的基线鸡蛋挑战之前以及在一小部分患者的口服鸡蛋挑战之后测试肠道渗透性。还将在 3 个月和 12 个月时测量肠道通透性，并将其与口服卵激发结果、粪便和血清抗卵 IgE 和抗卵 IgG 抗体水平相关。